Researchers explore association between SSRI exposure in late pregnancy and risk of PPHN

Use of antidepressants late in pregnancy has been controversial since the FDA issued a Public Health Advisory in 2006 warning that the use of antidepressants in late pregnancy may increase risk of persistent pulmonary hypertension of the newborn (PPHN), a condition that typically occurs in term or near-term infants and presents within hours of birth with severe respiratory failure requiring intubation and mechanical ventilation. The 2006 public health advisory was based on a single epidemiologic study that found a six-fold increase in risk associated with exposure to selective serotonin reuptake inhibitors (SSRI), commonly prescribed antidepressants, after the twentieth week of pregnancy. Based on a review of additional studies with conflicting findings, the FDA concluded in 2011 that it was premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN, and updated the advisory accordingly.

Given the ongoing controversy regarding the association between SSRI exposure in late pregnancy and the risk of PPHN, researchers from Brigham and Women's Hospital (BWH) and the Harvard T.H. Chan School of Public Health examined the risk of PPHN associated with both SSRI and non-SSRI antidepressants in a large cohort of publicly insured pregnant women across the United States. In new findings published in JAMA on June 2, 2015, researchers demonstrate that while the possibility of an increased risk of PPHN associated with maternal use of antidepressants in late pregnancy cannot be entirely excluded, the absolute risk is small and the risk increase, if present, appears more modest than suggested in previous studies.

"Clinicians and patients need to balance the potential small increase in the risk of PPHN, along with other risks that have been attributed to SSRI use during pregnancy, with the benefits attributable to these drugs in improving maternal health and well being," said Krista Huybrechts, MS. PhD, corresponding author of the study and epidemiologist in the Division of Pharmacoepidemiology and Pharmacoeconomics at BWH.

The cohort study included 3,789,330 pregnant women enrolled in Medicaid from two months or less after the date of last menstrual period through at least one month after delivery, of which 128,950, or 3.4 percent, filled at least one prescription for an antidepressant late in pregnancy. Among these women, 102,179 or 2.7 percent used an SSRI and 26,771 or 0.7 percent a non-SSRI antidepressant. The reference group consisted of women without exposure to antidepressants at any time during pregnancy.

Overall, 20.8 per 10,000 infants not exposed to antidepressants during the last 90 days of pregnancy had PPHN compared with 31.0 per 10,000 infants exposed to antidepressants. This higher risk among exposed infants was observed for both SSRI (31.5 per 10,000 infants) and non-SSRI (29.1 per 10,000 infants) antidepressants, representing a 40 to 50 percent increase in risk. After accounting for differences in the characteristics of women who did and did not take antidepressants, there was no longer a significant increase in the risk of PPHN associated with SSRI or non-SSRI antidepressants.

The findings in the largest cohort studied to date suggest that the risk of PPHN associated with late pregnancy exposure to SSRI antidepressants, if present, is smaller than previous studies have reported. Additionally, no evidence was found of a significantly increased risk associated with non-SSRI antidepressant medication use.